1,1'-Carbonyldiimidazole → 4-((2-cyanoadamantan-2-yl)methoxy)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamide

HRID 1849774Notes

Reaction equation

HRID 1849774 reaction equation
[C:1]([C:3]1([CH2:13][O:14][C:15]2[C:23]([CH:24]3[CH2:26][CH2:25]3)=[CH:22][C:18]([C:19]([OH:21])=O)=[C:17]([F:27])[CH:16]=2)[CH:10]2[CH2:11][CH:6]3[CH2:7][CH:8]([CH2:12][CH:4]1[CH2:5]3)[CH2:9]2)#[N:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:40][S:41]([NH2:44])(=[O:43])=[O:42].N12CCCN=C1CCCCC2>O1CCCC1.C(OCC)(=O)C>[C:1]([C:3]1([CH2:13][O:14][C:15]2[C:23]([CH:24]3[CH2:25][CH2:26]3)=[CH:22][C:18]([C:19]([NH:44][S:41]([CH3:40])(=[O:43])=[O:42])=[O:21])=[C:17]([F:27])[CH:16]=2)[CH:10]2[CH2:9][CH:8]3[CH2:7][CH:6]([CH2:5][CH:4]1[CH2:12]3)[CH2:11]2)#[N:2]

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 867036554-((2-Cyanoadamantan-2-yl)methoxy)-5-cyclopropyl-2-fluorobenzoic acid

Product 1

HCID 867036564-((2-cyanoadamantan-2-yl)methoxy)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamideYield 10%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-((2-cyanoadamantan-2-yl)methoxy)-5-cyclopropyl-2-fluorobenzoic acid (0.17 g, 0.45 mmol) in anhydrous tetrahydrofuran (5 mL) was added 1,1′-carbonyldiimidazole (0.15 g, 0.89 mmol). The reaction solution was heated to reflux under a nitrogen atmosphere for 15 minutes and cooled to ambient temperature. To this reaction solution methanesulfonamide (0.10 g, 1.05 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.22 mL, 1.40 mmol) was added. The mixture was stirred at ambient temperature for 2.5 hours, then diluted with ethyl acetate (10 mL), washed with 1 M hydrochloric acid (2×10 mL) and brine (2×10 mL). The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford the title compound as a colorless powder (0.019 g, 10%): 1H NMR (300 MHz, DMSO-d6) δ 11.94 (br s, 1H), 7.16-7.12 (m, 2H), 4.46 (s, 2H), 3.31 (s, 3H), 2.16-1.79 (m, 11H), 1.70-1.61 (m, 4H), 0.90-0.84 (m, 2H), 0.69-0.64 (m, 2H); MS (ES−) m/z 445.2 (M−1).

Workup

  1. temperatureThe reaction solution was heated
  2. temperatureto reflux under a nitrogen atmosphere for 15 minutes
  3. washwashed with 1 M hydrochloric acid (2×10 mL) and brine (2×10 mL)
  4. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ca14dba88c8641bb971e7470ee965635
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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